1977; Boyd et al. 1980; Armstrong et al. 1981). Therefore, the determination of the
stereoselective toxicity of the prochiral BaP and its transformation products are an
important aspect, and hence, some papers have been published on this issue. Levin
et al. (1977) reported the carcinogenic toxicity of trans-7,8-dihydroxy-7,8dihydrobenzo(a)pyrene (BP-7,8-dihydrodiol) on mice skin by a two-phase tumorigenesis system. The dose given (single application) on the backs of CD-1 mice
were 200, 100 and 50 nanomoles of the (+)- and (–)-enantiomers, respectively.
Wood et al. reported the differences in the mutagenicity of the enantiomers
of diastereoisomeric benzo(a)pyrene-7,8-diol-9,10-epoxides. In Chinese hamster
cell, (+)-BP-7β,8α-diol-9α,10α-epoxides was four times more toxic than its (–)enantiomer. By contrast, (–)-7β,8α-diol-9α,10α-epoxide was two times more toxic
than its (+)-enantiomer in TA 100 of Salmonella typhimurium and strains TA 98.
Moriya et al. (1996) used a site-specific approach to investigate the mutagenic
potential of (+)- and (À)-trans-anti-benzo[a]pyrene diol epoxide (BPDE) DNA
adducts. Oligodeoxyribonucleotides (
50 TCCTCCTG 1 G 2 CCTCTC), modified at the
exocyclic amino groups of G 1 or G 2 , were incorporated into a single-stranded shuttle
vector and introduced into Escherichia coli or simian kidney (COS) cells. This
experimental system permits translesional synthesis to proceed in the absence of
DNA repair. The presence of (+)- or (À)-BPDE-N
2 -dG adducts strongly inhibited
translesional synthesis in E. coli; induction of cellular SOS functions reduced this
blocking effect. Vectors containing (+)-BPDE adducts at G 1 or G 2 generated mutation frequencies of 19% and 3%, respectively; these values were not altered significantly by induction of SOS functions. In COS cells, (+)-BPDE-modified vectors
generated mutation frequencies of 13% at G 1 and 45% at G 2 . In E. coli, the (À)BPDE adduct generated mutation frequencies of 2% at G 1 and G 2 and, in COS
cells, 13% at G 1 and 21% at G 2 . The predominant mutations in E. coli and COS cells
were G!T transversions targeted to the site of the lesion; however, when G 2 was
modified, a significant number of targeted G!A and G!C mutations were
observed in COS cells. The authors concluded from this study that (+)- and (À)BPDE-N
2 -dG adducts pair preferentially to dCMP and dAMP during translesional
synthesis in a process that is strongly influenced by the stereochemistry of the
adduct, by the bases flanking the lesion and by host cell factors.
A selection of related reports on stereoselective toxicity of PAH-related compounds is available for the interested reader in recent publications (Smithgall et al.
1986, 1988; Lai et al. 1989; Platt et al. 1990; Luch et al. 1999; Driscoll et al. 2003;
Moody et al. 2003; Hecht and Hochalter 2014).
10.2.6 Other Xenobiotics
In addition to the selected chiral contaminants summarised above, some other chiral
molecules are present in the environment and may cause damage to the ecosystem.
For example, the toxicological information on specific chlorobornanes (Toxaphene
®
compounds, see earlier information, Chap. 3) is rare, but some papers have appeared
10.2 Toxicity of Chiral Pollutants
287
stereoselective toxicity of the prochiral BaP and its transformation products are an
important aspect, and hence, some papers have been published on this issue. Levin
et al. (1977) reported the carcinogenic toxicity of trans-7,8-dihydroxy-7,8dihydrobenzo(a)pyrene (BP-7,8-dihydrodiol) on mice skin by a two-phase tumorigenesis system. The dose given (single application) on the backs of CD-1 mice
were 200, 100 and 50 nanomoles of the (+)- and (–)-enantiomers, respectively.
Wood et al. reported the differences in the mutagenicity of the enantiomers
of diastereoisomeric benzo(a)pyrene-7,8-diol-9,10-epoxides. In Chinese hamster
cell, (+)-BP-7β,8α-diol-9α,10α-epoxides was four times more toxic than its (–)enantiomer. By contrast, (–)-7β,8α-diol-9α,10α-epoxide was two times more toxic
than its (+)-enantiomer in TA 100 of Salmonella typhimurium and strains TA 98.
Moriya et al. (1996) used a site-specific approach to investigate the mutagenic
potential of (+)- and (À)-trans-anti-benzo[a]pyrene diol epoxide (BPDE) DNA
adducts. Oligodeoxyribonucleotides (
50 TCCTCCTG 1 G 2 CCTCTC), modified at the
exocyclic amino groups of G 1 or G 2 , were incorporated into a single-stranded shuttle
vector and introduced into Escherichia coli or simian kidney (COS) cells. This
experimental system permits translesional synthesis to proceed in the absence of
DNA repair. The presence of (+)- or (À)-BPDE-N
2 -dG adducts strongly inhibited
translesional synthesis in E. coli; induction of cellular SOS functions reduced this
blocking effect. Vectors containing (+)-BPDE adducts at G 1 or G 2 generated mutation frequencies of 19% and 3%, respectively; these values were not altered significantly by induction of SOS functions. In COS cells, (+)-BPDE-modified vectors
generated mutation frequencies of 13% at G 1 and 45% at G 2 . In E. coli, the (À)BPDE adduct generated mutation frequencies of 2% at G 1 and G 2 and, in COS
cells, 13% at G 1 and 21% at G 2 . The predominant mutations in E. coli and COS cells
were G!T transversions targeted to the site of the lesion; however, when G 2 was
modified, a significant number of targeted G!A and G!C mutations were
observed in COS cells. The authors concluded from this study that (+)- and (À)BPDE-N
2 -dG adducts pair preferentially to dCMP and dAMP during translesional
synthesis in a process that is strongly influenced by the stereochemistry of the
adduct, by the bases flanking the lesion and by host cell factors.
A selection of related reports on stereoselective toxicity of PAH-related compounds is available for the interested reader in recent publications (Smithgall et al.
1986, 1988; Lai et al. 1989; Platt et al. 1990; Luch et al. 1999; Driscoll et al. 2003;
Moody et al. 2003; Hecht and Hochalter 2014).
10.2.6 Other Xenobiotics
In addition to the selected chiral contaminants summarised above, some other chiral
molecules are present in the environment and may cause damage to the ecosystem.
For example, the toxicological information on specific chlorobornanes (Toxaphene
®
compounds, see earlier information, Chap. 3) is rare, but some papers have appeared
10.2 Toxicity of Chiral Pollutants
287